公开(公告)号：EP2726100A2

公开(公告)日：2014-05-07

申请号：EP12803745.4

申请日：2012-06-13

申请人： Merrimack Pharmaceuticals, Inc. ,  SANOFI

发明人： KUBASEK, William ,  MOYO, Victor ,  PEARLBERG, Joseph ,  TABAH-FISCH, Isabelle ,  MACBEATH, Gavin

IPC分类号： A61K39/395

CPC分类号： A61K39/3955 ,  A61K31/337 ,  A61K39/39558 ,  A61K2039/545 ,  C07K16/32 ,  A61K2300/00

摘要： Provided are methods and compositions for clinical treatment of advanced gynecological cancers using anti-ErbB3 antibodies combined with paclitaxel.

公开(公告)号：EP3087394A2

公开(公告)日：2016-11-02

申请号：EP14830927.1

申请日：2014-12-29

申请人： Merrimack Pharmaceuticals, Inc.

发明人： ADIWIJAYA, Bambang ,  CZIBERE, Akos ,  KUBASEK, William ,  MACBEATH, Gavin ,  MOULIS, Sharon ,  NERING, Rachel ,  NIE, Lin ,  YARAR, Defne

IPC分类号： G01N33/574

CPC分类号： C07K16/2863 ,  A61K31/337 ,  A61K39/3955 ,  C07K16/3015 ,  C07K16/3023 ,  C07K16/3069 ,  C07K2317/21 ,  C07K2317/34 ,  C07K2317/56 ,  C07K2317/565 ,  C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/112 ,  C12Q2600/158 ,  G01N33/574 ,  G01N2333/71 ,  G01N2800/52

摘要： Provided are methods for optimizing therapy of, treating a patient having, or selecting (identifying) patients who will benefit from treatment for, a cancer (e.g., a non-hematological cancer; e.g., a gynecological cancer). The methods comprise determining whether the patient will benefit from treatment with an ErbB3 inhibitor (e.g., an anti-ErbB3 antibody), with or without either a taxane or an aromatase inhibitor, or with a taxane or an aromatase inhibitor in the absence of an ErbB3 inhibitor, based on levels of particular biomarkers and combinations of biomarkers measured in a biological sample obtained from the patient. The methods further comprise optimizing the patient's therapy, selecting the patient for treatment, or treating the patient accordingly. In various aspects the biological samples are sections of a biopsy (e.g., a formalin fixed paraffin embedded biopsy). In other aspects the biomarkers are proteins and/or nucleic acids. In other aspects the biomarkers function in ErbB-mediated signal transduction.

摘要翻译： 本发明提供用于优化的治疗，治疗患有，或选择的方法（确定）的患者谁将从治疗，癌症受益（E. G.，非血液癌症，E. G.，妇科癌症）。 该方法包括确定采矿患者是否会从与ErbB3抑制剂（例如，抗ErbB3抗体）治疗中受益，具有或不具有无论是紫杉烷或芳香酶抑制剂，或与紫杉烷或在不存在的ErbB3的芳香酶抑制剂 抑制剂，基于从患者获得的生物样品中测量的生物标记物的生物标记物和特定的组合的水平。 该方法还包括优化患者的治疗，选择对患者进行治疗，或以此对待病人。 在各种方面中的生物样品是活检（E. G.，福尔马林固定的石蜡包埋的切片）的部分。 在其它方面，生物标记物是蛋白质和/或核酸。 在其它方面，生物标志物的ErbB介导的信号转导作用。

公开(公告)号：EP2318548B1

公开(公告)日：2013-10-16

申请号：EP09791584.7

申请日：2009-08-17

申请人： Merrimack Pharmaceuticals, Inc.

发明人： SCHOEBERL, Birgit ,  HARMS, Brian ,  GIBBONS, Francis, David ,  FITZGERALD, Jonathan, Basil ,  ONSUM, Matthew, David ,  NIELSEN, Ulrik ,  KUBASEK, William

IPC分类号： C12Q1/68 ,  C07K16/32

CPC分类号： G01N33/6893 ,  A61K2039/505 ,  C07K16/2863 ,  C07K16/32 ,  C07K2317/31 ,  C12Q1/6809

公开(公告)号：EP2686015A2

公开(公告)日：2014-01-22

申请号：EP12714108.3

申请日：2012-03-15

申请人： Merrimack Pharmaceuticals, Inc.

发明人： GARCIA, Gabriela ,  KUBASEK, William ,  LAHDENRANTA, Maria, Johanna ,  MACBEATH, Gavin ,  MCDONAGH, Charlotte ,  MOYO, Victor ,  ONSUM, Matthew, David ,  SEVECKA, Mark ,  WAINSZELBAUM, Marisa ,  ZHANG, Bo ,  SCHOEBERL, Birgit

IPC分类号： A61K39/395 ,  A61K31/00 ,  A61K33/00 ,  C07K16/32

CPC分类号： C07K16/32 ,  A61K31/337 ,  A61K31/513 ,  A61K31/517 ,  A61K31/7068 ,  A61K33/24 ,  A61K39/39558 ,  A61K45/06 ,  A61K2039/505 ,  A61K2039/507 ,  A61K2039/55 ,  C07K16/2863 ,  C07K2317/31 ,  C07K2317/73 ,  C07K2317/76 ,  A61K2300/00

摘要： Provided are methods for overcoming resistance to an ErbB pathway inhibitor, such as an EGFR inhibitor or a HER2 inhibitor. The resistance may be acquired resistance to an EGFR inhibitor, such as acquired resistance to gefitinib. In the methods provided, a subject exhibiting resistance to an ErbB pathway inhibitor is selected and both an ErbB 3 inhibitor and a second ErbB pathway inhibitor are administered to the subject, such as an EGFR inhibitor or a HER2 inhibitor. Also provided are methods for inhibiting the growth of a tumor comprising a T790M EGFR mutation by contacting the tumor with an ErbB3 inhibitor and an EGFR inhibitor. Compositions for overcoming resistance to an ErbB pathway inhibitor, comprising both an ErbB 3 inhibitor and a second ErbB pathway inhibitor, such as an EGFR inhibitor or a HER2 inhibitor, are also provided.

公开(公告)号：EP2318548A2

公开(公告)日：2011-05-11

申请号：EP09791584.7

申请日：2009-08-17

申请人： Merrimack Pharmaceuticals, Inc.

发明人： SCHOEBERL, Birgit ,  HARMS, Brian ,  GIBBONS, Francis, David ,  FITZGERALD, Jonathan, Basil ,  ONSUM, Matthew, David ,  NIELSEN, Ulrik ,  KUBASEK, William

IPC分类号： C12Q1/68 ,  C07K16/32

CPC分类号： G01N33/6893 ,  A61K2039/505 ,  C07K16/2863 ,  C07K16/32 ,  C07K2317/31 ,  C12Q1/6809

摘要： The invention provides methods for treating patients which methods comprise methods for predicting responses of cells, such as tumor cells, to treatment with therapeutic agents. These methods involve measuring, in a sample of the cells, levels of one or more components of a cellular network and then computing a Network Activation State (NAS) or a Network Inhibition State (NIS) for the cells using a computational model of the cellular network. The response of the cells to treatment is then predicted based on the NAS or NIS value that has been computed. The invention also comprises predictive methods for cellular responsiveness in which computation of a NAS or NIS value for the cells (e.g., tumor cells) is combined with use of a statistical classification algorithm. Biomarkers for predicting responsiveness to treatment with a therapeutic agent that targets a component within the ErbB signaling pathway are also provided.

公开(公告)号：EP2704746A2

公开(公告)日：2014-03-12

申请号：EP12782207.0

申请日：2012-05-04

申请人： Merrimack Pharmaceuticals, Inc.

发明人： ONSUM, Matthew, David ,  NIYIKIZA, Clet ,  MOYO, Victor ,  KUBASEK, William ,  CZIBERE, Akos

IPC分类号： A61K39/395 ,  A61K38/16 ,  A61K38/17 ,  A61P35/00

CPC分类号： C07K16/32 ,  A61K31/517 ,  A61K31/5377 ,  A61K38/005 ,  A61K38/16 ,  A61K38/17 ,  A61K39/395 ,  A61K39/39558 ,  A61K45/06 ,  A61K2039/505 ,  A61K2039/545 ,  C07K2317/90 ,  A61K2300/00

摘要： Methods are disclosed for preventing toxic drug-drug interactions during combination cancer therapy with a drug that is an anti-ErbB3 agent, such as an anti-ErbB3 antibody, together with a drug that is a tyrosine kinase inhibitor and/or a drug that binds to alpha- 1 acid glycoprotein (e.g., erlotinib). Health care practitioners obtaining any one of the drugs are warned that when co-administering the drug that is an anti-ErbB3 agent with either or both of a drug that is a tyrosine kinase inhibitor and a drug that binds to alpha- 1 acid glycoprotein, at least one of the co-administered drugs should be administered using a reduced dosage to prevent toxicity. In a reduced dosage, the amount of drug administered per unit time is reduced as compared to a dose that would be administered if the drug was administered as monotherapy. The reduced dosage can be, for example, a reduced drug dose or a reduced drug dosing frequency, or both. Compositions useful in practicing the disclosed methods are also provided.

公开(公告)号：EP2683741A2

公开(公告)日：2014-01-15

申请号：EP12711080.7

申请日：2012-03-12

申请人： Merrimack Pharmaceuticals, Inc.

发明人： GARCIA, Gabriela ,  KUBASEK, William ,  MOYO, Victor ,  MACBEATH, Gavin

IPC分类号： C07K16/32 ,  A61K39/395 ,  A61P35/00

CPC分类号： A61K39/39558 ,  A61K31/4196 ,  A61K31/5685 ,  A61K45/06 ,  A61K2039/505 ,  C07K16/32 ,  C07K16/468 ,  A61K2300/00

摘要： Provided are methods of suppressing growth of hormone refractory breast tumors by contacting tumor cells with an ErbB3 inhibitor, preferably an anti-ErbB3 antibody. Also provided are methods for treating hormone refractory breast cancer in a patient by administering to the patient an inhibitor of heregulin binding to ErbB3 or to ErbB2/ErbB3 heterodimer, which inhibitor is an anti-ErbB3 antibody or an anti-ErbB2 antibody. The treatment methods can further comprise selecting a patient having a hormone refractory breast cancer and then administering the inhibitor to the patient. The treatment methods may also comprise administering an estrogen receptor antagonist, or an aromatase inhibitor to the patent and may at further comprise administering to the patient at least one additional anti-cancer agent that is not an ErbB3 inhibitor, an estrogen receptor antagonist, or an aromatase inhibitor to the patient in combination with the ErbB3 inhibitor.